Avian-virus-like receptor specificity of the hemagglutinin impedes influenza virus replication in cultures of human airway epithelium

作者：Matrosovich Mikhail^*; Matrosovich Tatyana; Uhlendorff Jennifer; Garten Wolfgang; Klenk Hans Dieter

来源：Virology, 2007, 361(2): 384-390.

DOI：10.1016/j.virol.2006.11.030

• influenza
• pandemics
• host range
• reverse genetics
• sialic acid
• receptor specificity
• cell tropism
• replication efficiency
• human airway epithelial cultures

A non-optimal receptor-binding specificity of avian influenza viruses is believed to hamper their replication in humans; however, the magnitude of this restriction remains undefined. Here we generated recombinant viruses, R1 and R2, that differed solely by two amino acids in the receptor-binding site of their hemagglutinin (HA). RI harbored the original HA of the pandemic human virus A/Hong Kong/1/68 (H3N2), whereas R2 was the L226Q/S228G HA mutant with avian-virus-like receptor specificity. In differentiated cultures of human tracheo-bronchial epithelial cells, RI preferentially infected non-ciliated cells, whereas R2 predominantly infected ciliated cells indicating that cell tropism was determined by the viral receptor specificity. In the course of multi-cycle replication in these cultures, R2 spread less efficiently and grew to 2-10-fold lower titers than did R I. These results for the first time estimate the level of receptor-dependent restriction of avian influenza viruses in human airway epithelium. They support a theory that alteration of the receptor specificity of an avian virus could facilitate its human-to-human transmission.

• 出版日期2007-5-10
• 单位河北医科大学